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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 307 records · Page 17Linked to original sources
PubMed1992

Differences in GTPase-activating protein activity between liver tumors and normal liver tissue in mice.

The intrinsic GTPase activity of the cellular protein p21ras is strongly increased by two cytosolic proteins, the GTPase-activating protein (GAP) produced by the neurofibromatosis type 1 gene (NF1-GAP) and a GAP of 120 kDa molecular mass (p120-GAP). The GAP-mediated stimulation of p21ras GTPase activity was measured in cytosol obtained from carcinogen-induced liver tumors and normal liver tissues of mice of two strains, namely C3H/He and C57BL/6J. For this purpose, cytosolic extracts were incubated with recombinant human p21ras complexed to [gamma-32P]GTP and the time-dependent decrease in p21ras bound radioactivity was measured. Liver cytosolic extracts mediated an increase in the GTPase activity of wild-type p21ras. There were great differences between tumor and normal tissues in the maximal velocity (Vmax) and in the apparent Michaelis constant (KM) of the p21ras GTPase reaction. Both Vmax and apparent KM were decreased in the liver tumors. Cytosolic extracts isolated from liver tumors that harbored point mutations in codon 61 of the c-H-ras gene did not differ in their activity from extracts obtained from non-mutated liver tumors. Since both GAP proteins are important cellular regulators of the ras signaling pathway and probably also effectors of p21ras, the observed differences in GAP activity may be of relevance for the tumorigenic process in mouse liver.

Animals↗
PubMed1992

The influence of ethanol on pancreatic blood flow in cats with chronic pancreatitis.

BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis.

Animals↗
PubMed1991

A simple and rapid slide blot method to quantify cytokine-mRNA in small numbers of lymphocytes.

In this study we describe an in situ hybridization protocol suitable for the measurement of interleukin mRNAs in small numbers of cells in suspension. In this procedure defined numbers of such cells are coated onto defined areas of microscopic slides using LAB-TEK tissue culture chamber slides. 32P-labelled oligonucleotides are then hybridized to them in situ. Binding of the probes is measured by autoradiography using X ray film followed by densitometry (slide blot) or, as in standard in situ protocols, by exposure to photoemulsion. In experiments designed to demonstrate the specificity and feasability of this protocol, peripheral blood T cells were activated with mitogenic stimuli and oligonucleotide probes specific for IL-2, IFN-gamma, or a control probe (IL-2 random) were hybridized to them. Both lymphokine genes were found to be transcribed in two discrete phases with the first peak at 12 h and another peak 48 h after stimulation, as measured semi-quantitatively on a per cell basis using X ray film exposure. The proposed experimental protocol supports the advantages of X ray film autoradiography such as rapidity, simplicity and the objectivity of densitometric evaluation, but also permits microscopic evaluation of individual cells as performed in classical in situ hybridization protocols using photoemulsion.

Base Sequence↗
PubMed1991

[Dynamic computed tomography of the neck as an alternative to carotid arteriography].

Spontaneous dissection of the internal carotid artery is a frequent cause of acute ischemic cerebrovascular accidents in young patients. The diagnosis is usually based on arteriographic findings. We report a 31-year-old man with spontaneous dissection of the internal carotid artery in the neck, and compare the findings on arteriography with those on contrast enhanced, dynamic computed tomography (DCT) of the cervical and intracranial portion of the carotid system DCT may play an important role in the diagnosis of dissection of the carotid artery, and in its follow-up, as an alternative to arteriography.

Adult↗
PubMed1991

Mutational activation of the c-Ha-ras gene in liver tumors of different rodent strains: correlation with susceptibility to hepatocarcinogenesis.

The frequency and pattern of mutations at codon 61 of the c-Ha-ras gene have been analyzed in 195 liver tumors and 132 precancerous liver lesions from various rodent strains with differing susceptibility to hepatocarcinogenesis. By using the polymerase chain reaction and allele-specific oligonucleotide hybridization, C----A transversions at the first base and A----T transversions or A----G transitions at the second base of c-Ha-ras codon 61 were detected in 20-60% of spontaneous or carcinogen-induced liver tumors of the C3H/He, CBA, CF1, and B6C3F1 mouse strains, which are highly susceptible to hepatocarcinogenesis. No such mutations, however, could be found in any of the 31 liver tumors of the insensitive C57BL/6J and BALB/c mouse strains or in any of the 35 liver tumors of the comparatively resistant Wistar rat. Further analyses of c-Ha-ras codon 12 mutations in liver tumors from the three insensitive rodent strains also failed to give any positive results. In early precancerous liver lesions, c-Ha-ras codon 61 mutations were found in 13-14% of lesions of the sensitive C3H/He and B6C3F1 mouse strains but not in any of the 34 lesions of the insensitive C57BL/6J mouse. Taken together, our results indicate a close correlation between the mutational activation of the c-Ha-ras gene in liver tumors of the different rodent strains and their susceptibility to hepatocarcinogenesis, whereby the mutations appear to provide a selective growth advantage, leading to a clonal expansion of the mutated liver cell population, only in livers of sensitive but not of insensitive strains.

Animals↗
PubMed1991

Paradoxical anticonvulsant activity of the gamma-aminobutyrate antagonist bicuculline methiodide in the rat striatum.

Bicuculline methiodide (BMI), a gamma-aminobutyrate (GABA) antagonist, is a powerful convulsant agent when injected into the cerebral ventricles, amygdala, hippocampus, thalamus, neocortex, and deep prepiriform cortex in rats. In contrast, bilateral microinjection of BMI into the rat striatum confers protection against seizures induced by the cholinergic agonist pilocarpine (380 mg/kg, i.p.), with an ED50 of 94 fmol (range 45-195 fmol). No topographical variation in the anticonvulsant action of BMI was detected throughout rostrocaudal and dorsoventral aspects of the striatum. The anticonvulsant action of BMI in the striatum was reversed by coadministration of the GABA agonist muscimol or by blocking GABA-mediated inhibition in either the substantia nigra pars reticulata or in the entopeduncular nucleus. The results show that blockade of GABA-mediated inhibition in the striatum has a powerful anticonvulsant effect in the pilocarpine model, suggesting that GABAergic transmission in the striatum modulates the seizure propagation in the forebrain.

Animals↗
PubMed1991

A deletion mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) locus: Delta I507.

During the development of an amplification refractory mutation system (ARMS) assay for the detection of the Delta F508 mutation and corresponding normal locus in cystic fibrosis we discovered a family in which a further variant of the sequence exists. PCR amplification and direct sequencing of a region of exon 10 of the CFTR locus indicated the deletion of the three base pairs encoding isoleucine or isoleucine, or possibly the presence of a single base substitution in conjunction with the Delta F508 mutation. The resulting protein has a deletion of an isoleucine residue at position 507 as opposed to the previously described deletion of phenylalanine at position 508. We conclude that the loss of an isoleucine residue at position 507 (Delta I507) is another defective variant of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene product.

Amino Acid Sequence↗
PubMed1991

Effects of polychlorinated biphenyls in rat liver: correlation between primary subcellular effects and promoting activity.

In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequently treated once weekly with polychlorinated biphenyls (150 or 15 mumol/kg body wt) for a total of 8 weeks. Additional groups of rats were administered 3,3',4,4'-tetrabromobiphenyl or 3-methylcholanthrene (8 weekly injections of 15 or 150 mumol/kg body wt, respectively) or were given phenobarbital (0.05% in the diet) until the end of the experiment. Reference groups were treated with the various test compounds without prior initiation. One week and 9 weeks after cessation of promoter treatment rats were killed and the volumetric fraction of enzyme-altered foci characterized by changes in adenosine triphosphatase and gamma-glutamyl transpeptidase activity was determined as a means to quantitatively assess the extent of preneoplastic response in this organ. Out of the series of polyhalogenated biphenyls tested, promoting effects were seen with the following compounds: 2,2',4,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 2,3,4,4',5-pentachlorobiphenyl, and 3,3',4,4'-tetrabromobiphenyl, whereas no significant effects were obtained with 4-monochlorobiphenyl. In rats not treated with DEN, the two strongly promoting agents 2,3,4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrachlorobiphenyl also significantly increased the volume fraction of enzyme-altered foci over the respective controls when analyzed at the second time point of investigation. In parallel experiments, induction of liver growth and of microsomal cytochrome P450 content in liver was found to correlate well with the promoting activity of the various xenobiotics, suggesting that these parameters may be used to predict the promoting activity of polyhalogenated biphenyls in a short term assay.

Adenosine Triphosphatases↗
PubMed1991

Effects of polychlorinated biphenyls in rat liver: quantitative analysis of enzyme-altered foci.

The promotional effect of various polychlorinated biphenyls and phenobarbital on enzyme-altered lesions in the rat liver was quantified within the framework of the two-stage carcinogenesis model of Moolgavkar and colleagues. The experiment analyzed here followed an initiation-promotion protocol in which female Wistar rats were initiated with diethylnitrosamine (DEN) at 10 mg/kg body wt for 10 days followed by a 8-week period of promoter treatment with various cytochrome P450 isoenzyme inducing and noninducing compounds. This analysis included 4-monochlorobiphenyl, 2,2',4,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl and 3-methylcholanthrene, all administered at 150 mumol/kg body wt, and phenobarbital which was administered continuously in the diet at 0.05% until termination. Animals were killed either 1 or 9 weeks after the end of treatment and their livers were examined for enzyme histological alterations. Focal transections were classified as falling into three phenotypic categories: ATPase dominant, GGT dominant, or ATPase plus GGT (coextensive). A quantitative method was used to analyze the data consisting of the number and sizes of the focal transections. The number of cells altered by the DEN treatment and cell kinetic parameters measuring the promotional effect of the various compounds were estimated. On the basis of these estimates, we computed the number of nonextinct altered foci and their volume fraction as functions of time. We found that foci exhibiting the coextensive phenotype respond most efficiently to promoter treatment, while GGT dominant foci respond weakly to all the promoters with the exception of 3-MC. For phenobarbital, we observed a significant slowing of focal cell proliferation over time.

Adenosine Triphosphatases↗
PubMed1991

Effect of varying the concentration of phenobarbital and its duration of treatment on the evolution of carcinogen induced enzyme-altered foci in rat liver.

The present study was aimed to investigate whether the promoting activity of phenobarbital in rodent liver is related to its daily dose level and duration of treatment or rather to its total dose administered. For this purpose groups of female Wistar rats were treated for 5 consecutive days with an initiating dose of 10 mg/kg body weight N-nitrosodiethylamine. Subsequently, rats were given phenobarbital-sodium (PB) in their drinking water at concentrations of 20, 50, 100 and 200 mg/l for varying lengths of time, such that the total dose of xenobiotic was very similar throughout the different treatment groups ranging from approximately 950 to 1100 mg/kg body weight. The number and volume fraction of lesions negative for the marker enzyme adenosine triphosphatase in liver were subsequently scored as a means to determine the carcinogenic response in this organ. Slight promoting effects of PB were only seen at the lowest concentration of 20 mg/l, whereas no significant effects were observed at 50 and 100 mg/l. At the highest concentration of 200 mg/l an inhibition of carcinogenic response was obtained. Although the effects seen in this study were only moderate, our data favour the idea that the promoting effects of PB depend on the actual concentration of the compound and the duration of treatment rather than on the total dose administered.

Adenosine Triphosphatases↗
PubMed1991

Variables affecting long-term memory of learning that a food is inedible in Aplysia.

Long-term memory of learning that a food is inedible was studied in Aplysia. Seven days after a single training session, animals retained significant memory, as measured by a number of parameters. A 2nd experiment demonstrated savings 3 weeks after 2 training sessions. Long-term memory was also found after training procedures were altered to resemble those more likely to occur in nature, such as training for only 10 min or training with ad-lib access to inedible food, with no experimenter intervention. The effects were determined of bilaterally sectioning the esophageal nerves that innervate the gut. Denervation of the gut blocked the ability to learn that food is inedible but did not affect memory after the task had already been learned.

Animals↗
PubMed1991

Language functions in progressive supranuclear palsy.

Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy.

Aged↗
PubMed1991

Mitochondria Isolated from NaCl-Adapted Tobacco Cell Lines (Nicotiana tabacum/gossii) Maintain Their Phosphorylative Capacity in Highly Saline Media.

The in vivo functioning of mitochondria isolated from two tobacco cell lines in suspension culture (Nicotiana tabacum/gossii), wild type, and NaCl-adapted (A190), has been compared in the face of rising external salinity. The O(2) uptake of both state 3 and state 4 mitochondria was progressively inhibited with increasing external NaCl concentration in the case of both lines. Phosphorylation, however, was maintained at a higher level in the case of A190 mitochondria, as indicated both by stability of ADP:O ratio and rate of incorporation of (32)Pi. The superior phosphorylation performance of A190 mitochondria also emerged when phosphorylation was calculated per reducing equivalent, but not per unit DeltamuH(+) (electrochemical potential gradient for protons). However, the overall DeltamuH(+) was maintained at a higher level in A190 mitochondria due to the fact that the depolarization accompanying increase in external NaCl concentration was compensated for in A190 mitochondria by an increase in the transmembrane pH gradient, but not in wild type mitochondria. Increased proton permeability of the inner membrane is among the probable causes suggested for the loss of phosphorylation ability in wild type mitochondria; in contrast, A190 mitochondria maintain better membrane integrity under saline stress.

Journal Article↗
PubMed1991

Different mechanisms underlie the long-latency stretch reflex response of active human muscle at different joints.

1. Stretch of voluntarily activated human muscle results in a reflex response consisting of short-latency (M1) and delayed long-latency (M2) components. The mechanism of the M2 response remains the subject of controversy. The present study tested the universality of the hypothesis that the M2 response results from the transmission of low-threshold muscle afferent input travelling over a long-loop supraspinal pathway. Muscle reflex responses resulting from imposed stretch were obtained from the first dorsal interosseus (FDI), biceps brachii (BB), triceps brachii (TB) and triceps surae (TS) muscles. 2. Patients suffering from Huntington's disease (HD) show a selective loss of FDI-M2 responses, with sparing of the M1. This has been attributed to disruption of supraspinal pathways as a part of the disease pathology. Accordingly, HD has been used in the present study as a model to test the universality of the long-loop hypothesis: if this is so, then HD patients with an absent FDI M2 should also fail to show an M2 response in other muscles. 3. It is shown that a group of HD patients in whom the FDI-M2 response was absent or residual developed clear M2 responses in the TB, BB and TS muscles following stretch sufficient to invariably evoke this component in normal subjects. 4. It is thus concluded that longer-latency stretch reflex components are not invariably mediated over long-loop supraspinal pathways, but that this mode of control is dominant only in muscles, such as those of the hand, whose function depends largely on direct cortical control.

Adult↗
PubMed1991

Evidence that low-threshold muscle afferents evoke long-latency stretch reflexes in human hand muscles.

1. The aim of the present study was to identify the type of spinal afferents involved in the generation of the long-latency response in intrinsic human hand muscles. Position-controlled extensions were imposed on the index finger or on the wrist of healthy subjects who were exerting a steady voluntary flexion force at the relevant joint. Averaged surface electromyographic (EMG) responses of the first dorsal interosseus muscle (FDI) or of the wrist flexors were evaluated with respect to latency and size. 2. Small transient angular displacements of the index finger (1 degree, as measured at the metacarpophalangeal joint), which are supposed to excite primary rather than secondary afferents, evoked two clearly discernible EMG responses with mean latencies of 32.3 ms (M1 response) and 54.7 ms (M2 response), respectively. The size of the M2 response exceeded the size of the M1 response by 60%. In the wrist flexors, transient stretch (1 degree) gave rise to a large M1 response (latency 22.8 ms) and a small, inconstent M2 response. 3. Small-amplitude vibration of the index finger elicited EMG responses in the FDI that were qualitatively and quantitatively similar to those seen in response to small transient stretches of the index finger. This was also true for fast ramp-and-hold stretches (stretch velocity 400 degrees/s, amplitude 5 degrees), whereas slow ramp-and-hold stretches (125 degrees/s, 5 degrees) elicited predominantly M2 responses. 4. In the FDI, the mechanical threshold of the M1 and M2 response to the transient angular displacement was approximately 0.15 degrees, with a tendency for the M2 response to appear at a lower threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Increased Fc-receptor-mediated clearance via reticuloendothelial system in patients with nephrotic syndrome.

Reticuloendothelial phagocytic cell function, which is an important participant in host defense, was investigated by studying the Fc-receptor-mediated clearance of IgG-anti-RhD-sensitized radiolabelled autologous erythrocytes in patients with nephrotic syndrome known to have an increased risk of infectious complications due to hypogammaglobulinemia. Patients with serum IgG concentrations less than 500 mg/dl had a significantly accelerated Fc-receptor-mediated clearance (t1/2 = 52 +/- 3.6 min) compared to patients with IgG levels greater than 500 mg/dl (t1/2 = 93 +/- 17 min) or healthy controls (t1/2 = 100 +/- 7.5 min). Serum IgG concentrations correlated significantly with Fc-receptor-mediated clearance (t1/2: r = 0.70; p = 0.035) in patients with nephrotic syndrome. These results indicate that Fc-receptor-mediated clearance by the reticuloendothelial system is enhanced in patients with nephrotic syndrome with low serum IgG concentrations and may, at least in part, compensate for reduced opsonic antibody concentration.

Adult↗